Malaria Drugs (Ceryak) Flashcards
Name artemisinins (2)
- artemether
- artesunate
Quinolines (3)
- chloroquine phosphate
- quinine sulfate/quinidine gluconate
- primaquine
Adjunctive with quinolines (2)
- doxycycline
- clindamycin
Artemisinins target species
P. falciparum and P. vivax
How do artemisinins function as anti-malaria
endoperoxide moeity (free radial production)
Artemisinins resistance due to
counterfeit drugs
Which artemisinin is given orally and which is IV/rectal?
Oral: artemether
IV/Rectal” artesunate
How are artemisinins absorbed, metabolized, and excreted
Rapid absorptions, metabolism (CYP), biliary excretion
Describe the artemisinin half life; prophylaxis?
Short! (1-2 hours); not useful for prophylaxis; not good as monotherapy
Artemisinin-based combo therapues (ACTs)
increase efficacy and decrease resistance
Artemisinin adverse effects
- generally well-tolerated, not recommended for children <5kg or during 1st trimester of pregnancy
- reduced RBC and neutrophils; transient heart block (rare, dose-related, reversible)
Coartem =
artemether and lumefantrine; which both target blood stages
What is beneficial about coartem?
large Vd and 4-5 day half-life
Coartem problem
substantial drug-drug interaction with antiretrovirals/protease inhibitors (may need to increase dose)
How should pts take ACTs?
with fatty food or whole milk (if pt vomits within 30 min, repeat dose)
What pts are ACTs contraindicated in?
Cardiac arrhythmias, cardiac disease
How do you get artesunate?
CDC!
Quinolines and related compounds mechansim
interfere with heme digestion
Chloroquine mechanism of action
- plasmodium digest host cell hemoglobin
- process releases large amts of heme, which is toxic to plasmodium
- normally, plasmodium polymerizes heme to nontoxic hemozoin
- chloroquine prevents polymerization to hemozoin
Chloroquine resistance
pfcrt mutation - increased drug efflux
Is chloroquine safe in pregnancy?
Yes!
Oral chloroquine adverse effects
- Visual disturbances
- pruritis in African descent
- rare hemolysis w/ pt w/ G6PD deficiency
- discoloration of nail beds/mucous membranes
Chloroquine parental doses > 5g
usually fatal!
-CV and CNS (irreversible retinopathy, arrhythmias, etc.)
What pt is chloroquine contraindicated in?
- pt w/ epilepsy/myasthenia gravis bc affects neuro-muscular transmission
- pt w/ psoriasis/porphyria cutanea tarda
Chloroquine caution in pt w/…
- pt w/ advanced liver or GI disease, neurological or blood disorders (G6PD deficiency)
- pt w/ cardiac dysarhythmias
What to avoid while taking chloroquine
- kaolin (clay mineral) and Ca2+/Mg2+ containing antacids (delay GI absorption)
- concomitant administration of cimetidine (inhibits metabolism of chloroquine)
Quinine use against…
chloroquine-R and MDR P. falciparum asexual blood stages, gametocyticidal against P. vivax and P.ovale
Quinine mechanism
interferes w/ heme digestion
What is different about IV quinine?
more potent/toxic
Quinine absorption, metabolism, excretion
Readily absorbed (good tissue distribution in CNS and placenta); hepatic metabolism CYP3A4; renal excretion
Quinine resistance
Pfmdr1 gene amplification (pumps out drug)
Quinine adverse effects (dose-related toxicities)
-cinchonism = tinnitus, deafness, visual disturbance, headache, nausea, vomiting, dizziness, postural hypotension (reversible)
Quinine adverse effects (hypersensitivity)
rash, urticaria, angioedema, bronchospams
-blackwater fever: severe hemolysis; hemoglobinemia
When do you stop quinine treatment?
Hemoglobinuria
Increased hemolysis with quinines in pt w/…
G6PD deficiency
Quinine contraindicated in pt w/…
pt w/ tinnitus/optic neurititis
Quinine caution in pt w/…
- pt w/ hypersensitivity (discontinue if evidence of hemolysis)
- pt w/ cardiac dysrhythmias
- pregnancy (possibly safe)
- decrease dose w/ renal insufficiency
- aluminum/magnesium-containing antacids delay GI absorption
- CYP3A4 inhibition
